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a saunas Parana rrcn ERNEST A, WW, F INDIANAPOLIS, INDIANA, ASSIGNQR T0 FARM DAVIS dc CQMPANY, 0F DETROIT, MIGHIGAIN, A CORPORATION.

ESWERS O]? MING-TQLUIG ACIDS AND QTHER SIMILAR CQMPQ'UNDS 0E SAID AGNES.

Ito Drawing tion of synthetic substances having the property of producing local anaesthesia, while at the same time being characterized by their small degree of irritation when applied to the tissues and also by a lower toricity than any other of the substances commonly used as local anaesthetics. I

The invention broadly stated, may he said to consist of anaesthetic compounds derived from (ii-substituted benzoic acids in which the essential substituents are the atomic aggroupments NH, and Cld Such disubstituted benzoic acids may be represented by substantially the formula:

may be represented by the formula:

R in which R is an allryl group and R1 may be either an alkyl group or a hydroien atom. 1 wish expressly to make clear t at my invention covers compounds in which the amino group itself contains no alkyd Specification of Letters Patent.

Patented Sept, 3 1), 191M190 Application filed July 29, 1918. %rial No. 247,319.

substituents, and in which any two nuclear hydrogen atoms in the benzoic acid constituent are replaced by the group NH and the alkyl radical CH,, forming an entirely diflerent series of compounds from those of Stolz, at cl, as will be readily appreciated by one versed in structural chemistry.

Specific embodiments of the invention are alkamin esters of amino-toluic acids and salts thereof as represented by substantially the following formula:

in which R is any bivalent hydrocarbon radical, R and R are alkyl radicals which may be alike or diderent, and X is a halogen atom, the NH,, and -CH groups being situated in any positions in the benzene rir%.

he allrainin esters of the amino-toluic acids are colorless, solids or viscous oils solidifying at low temperatures, as a rule readily soluble in the usual organic solvents, such as ether, alcohol, acetone, and benzene; only slightly soluble in water and such solution having an alkaline reaction to litmus. @n heating with mineral acids or alkalis, the allramin esters are hydrolyzed with the formation out an alkamin and amino-toluic acid. The allrarnin esters form salts with one equivalent of an acid, which salts are soluble in, water with a neutral reaction.

A. specific example of the alkamin esters belonging to this series is the diethylaminoethanol ester of ortho-amino-para-toluic acid having the formula:

which may he prepared as follows: Equal hill Elli

molecular proportions of ortho-nitro-paratoluyl chlorid and diethylaminoethanol are forming the hydrochlorid of the diethylaminoethanol ester of ortho-nitro-para-toluic acid as indicated. Ten parts by Weight of the latter substance are dissolved in a mixture of twenty-five parts by weight of hydrochloric acid (sp. gr. 1.2) and twenty parts by weight of alcohol, and the solution treated with twelve parts by weight of granulatel tin, keeping the temperature at about 35 The reaction progresses rapidly and is complete when there is no further tendency to warm itself spontaneously.- A colorless solution is obtained from which the tin is removed by precipitation with hydrogen sulfid. On -addition of sodium carbonate solution, the diethylaminoethanol ester of ortho-amino-para-toluic acid separates as an oil. When treated with one equivalent of hydrochloric acid it forms a hydroehlorid which is readily soluble .in water with a neutral reaction and crystallizes from a mixture of absolute alcohol and ether in colorless crystals melting at 1578 C.

Another specific example of the alkamin esters belonging to this series is the diethylaminoethanol ester of para-amino-orthotoluic acid which may be prepared in a manner analogous to that previously stated, that is, by the reduction of the diethylaminoethanol ester of para-nitro-ortho-toluic acid, which may be prepared by the reaction occurring when equal molecular proportions of para-nitro-ortho-toluyl chlorid and diethylaminoethanol are mixed. The diethylaminoethanol ester of para-amino-orthotoluic acid is precipitated from the reaction mixture as a colorless oil after the removal of the tin. When treated with one equivalent of hydrochloric acid it forms a hydrochlorid whichv is readily soluble in water with a neutral reaction and crystallizes from a mixture of absolute alcohol and ether in colorless crystals melting at 13940 G.

In an analogous manner other alkamin esters of other amino-toluic acids and other salts of said esters may be obtained.

Having thus described my invention, what I claim is 1. Alkamin esters of di-substituted benzoic acids in which the essential substituents -NH and CH may be located in any positions in the benzene ring.

mixed upon which they react according to the equation:

.HCl

2. Alkamin esters of amino-toluic acids.

3. The products represented by substantially the ollowing formula:

1\ B 1 5; R 0 000 NH --CH3 in which R is any bivalent hydrocarbon radical, R and R are alkyl radicals which maybe alike or different, and X is an acid anion, the NH and CH groups being situated in any position in the benzene ring.

4. As new porducts, the alkamin esters of ortho-amino-para-toluic acid, being colorless compounds, solids or viscous oils solidi-- fying at low temperatures, as arule readily soluble in the usual organic solvents, slightly the usual organic solvents, slightly soluble in Water with an alkaline reaction to litmus, decomposed when heated with hydrochloric acid or sodium hydroxid, into diethylaminoethanol and ortho-amino-para-toluic acid,

forming a salt with one equivalent of hydrochloric acid which crvstallizes from a mixture of absolute alcohol and ether in colorless crystal melting at 1578 centigrade and forms aqueous solutions of neu-- tral reaction which produce local anaesthesia with a relatively small degree of irritating "or toxic action.

In witness whereof I have hereunto set my hand and seal at Indianapolis this 8th day of July, A. D. nineteen hundred and eighteen.

Erma-sir A, WILDMAN. [1a. 5.

Witnesses:

HARoLn GRAY, ARTHUR L. WALTERS. 

